The aim of our proposed research is to investigate the physiological function of histamine and its mode of action in embryonic development and implantation. We have recently shown that the mammalian preimplantaton embryo has histamine forming capacity and that inerference with this function interrupts embryo development and implantation. Still unanswered is how histamine could be involved in these processes. On the basis of our findings and exploitation of the findings of other investigators, we propose that histamine produced by the embryo or released from the uterus by estrogen, stimulates phospholipase A2 activity, considered by many as the rate-limiting enzyme, which makes available free arachidonic acid for prostaglandin synthesis in the embryo and/or in the endometrium at the site of implantation. Histamine or prostaglandins, or both, in a cascade manner, then participate in embryo development and implantation. Radioimmunoassays and isotopic enzymatic assays will be used to study the formation of prostaglandins and histamine in the embryo and the uterus under different physiological and experimental conditions. The culture and transplantation of embryos will be used to answer physiological implications of histamine in embryogenesis and implantation. Progress in the development of novel methods of fertility regulation as well as in the area of control and prevention of abnormal development and birth defects will be advanced by information about early stages of embryogenesis and implantation. The proposed project is aimed at obtaining such information.